1. Field of the Invention
The present invention relates to the use of the active ingredient obtained from the green hull of the kukui nut as an antiviral agent, particularly for use in the novel treatment of viral infections, in particular herpes simplex type 1 and 2, herpes zoster, genital warts and chickenpox.
2. Description of Related Art
Viruses are smallest of parasites but biggest nuisance the human population encounters on daily basis. Viruses are intracellular molecular particles with a central core of nucleic acid and an outer cover of protein. For their reproduction, viruses are wholly dependent on the host cells.
Several hundred different viruses are know to cause infection in man. Because of their wide prevalence, they create important medical and public health problems. Included among them is the most common of all viral diseases, the cold often accompanied by cold sores, which alone is responsible for one billion episodes of disease every year in the United States alone. Also included are such highly infectious viral diseases as measles, chickenpox, very painful and unpleasant herpetic viral diseases caused by herpes simplex or herpes zoster and such deadly viral diseases as rabies. All these viruses are spread quickly by man himself, mainly via respiratory and enteric excretions or by contact. Moreover, some of the viruses are very resistant and persistent and some of them, for example herpes simplex viruses, once inside the body they never leave.
There is no simple treatment of viral diseases. They are not susceptible to antibiotics and there is no other available treatment of viral diseases other than by chemotherapy which inhibits viral replication in the host cells. The Merck Manual, 158-168 (1987). Examples of these chemical agents are idoxuridine (IDU) useful for treatment of herpes simplex keratitis and methisazone active against influenza A virus. The other known viral replication inhibitors are acyclovir, ribavirin, vidarabine, gancyclovir and adenine arabinoside (ARA-A). These, and other viral replication inhibitors, however, are known to be cytotoxic, hepatotoxic, neurotoxic, nephrotoxic and having teratogenic effect, i.e., causing birth defect. Virus Diseases, 1-6 (1978) Crown Publishers, N.Y.
Thus it would be highly desirable to have available a nontoxic, preferably naturally occurring material which would be effective against viruses in general and against those viruses which are most painful, uncomfortable, ungainly and debilitating, such as herpes simplex and herpes zoster.
Herpes simplex, also called fever blister and cold sore is one of the most prevalent viral infection. The infecting agent is the relatively large herpes simplex virus herpesvirus hominis (HVH). There are two HVH strains. Type-1 strain commonly causes herpes labialis located on a lip, and keratitis, an inflammation of the cornea. Type-2 is usually located on or around genital area and is generally transmitted primarily by direct contact with herpetic sore or lesions. Thus, herpes simplex virus type-1 occurs above the waist and herpes virus type-2 occurs below the waist.
Estimated frequency and location of oral (herpes simplex type-1) and genital (herpes simplex type-2) infections are about half million of primary cases of type-1 per year, with 98 million of recurrent cases per year in the United States alone. Of the genital type-2 cases, there are around 500,000 cases of primary genital herpes with 3-9 million of recurrent cases per year in the United States. Living With Herpes, 1-11, (1983), Doubleday and Company, N.Y.
Herpes simplex infection is recurrent infection characterized by the appearance on the skin or mucous membranes of single or multiple clusters of small vesicles, filled with clear fluid on slightly raised inflammatory bases. These symptoms usually accompany a flu or some such other state where the body resistance is low. Herpes simplex is very infectious and it is rapidly and easily transferable by contact.
Herpetic lesions may appear anywhere on the skin or mucosa, but are more frequent about the mouth, on the lips, on the conjunctiva and cornea, and on or around the genitalia. Following a short prodromal period of tingling discomfort or itching, small tense vesicles appear on the erythematous base. Single clusters vary in size from 0.1 to 1.5 cm. The vesicles persist for a few days, then begin to dry, forming a thin yellowish crust. Healing is long and usually begins 7-10 days after onset of the viral infection and is complete by about 21 days. Healing may be slower, with secondary inflammation, in moist body areas. Individual herpetic lesions usually heal completely but recurrent lesions at the same site may cause atrophy and scarring. It will be appreciated that the herpes simplex outside or inside mouth, lips, cheeks, chin and particularly on or around the genitalia is very painful and uncomfortable as it burns or itches, as well as ungainly, with an often open sore on the lip and, particularly as it does on recurrence, leaving the ugly lesions on or around lips.
As pointed out above, once present the virus herpes simplex never leaves. Although at about three weeks of herpes simplex infection the evidence of infection is no longer manifest, the virus has not been eradicated from the body; rather it remains in a dormant state in nerve tissue near the site of infection. In the case of oral, labial and facial herpes, the latent virus takes up residence in a nerve cluster called the trigeminal ganglion, located near the cheek bone. There are two factors that are important in viral reactivation - general health and stress. Since the medical science has not come up yet with a substance which is fully curative, the body is left on its own in limiting the viral activity. And of course, in organism weakened by ill health, infection, stress and other circumstance, the recurrence of herpes simplex viral infection is a serious problem. Moreover, once a virus takes over and develops into full fledged sore, it runs its course, submitting the victim to pain, itch and scarring connected with viral sores.
Thus, it would be very appreciated by the herpes virus carriers and victims, if there would be available non-toxic, but highly effective antiviral agent which would be able to suppress and alleviate immediately the first symptoms of the viral infection, i.e., swelling, tingling and itching which occurs on the site of sore before it develops into full fledged blister, and thus prevent the development of sore which could last up to three weeks and has high probability to leave a scar. Such agent would not only have appreciable therapeutic effect by inhibiting the development of painful sore of the individual but also prophylactic effect by terminating an infection spread to other people caused by highly transmittable stage of virus when blisters erupt and can easily be transmitted by air or on contact.
The type-2 of herpes simplex has even bigger and more severe, if possible, consequences. Due to its location on or around the genital area, the social stigma attaches of having this type of herpes infection categorized as a venereal disease. The viral disease itself is much the same as the herpes simplex type-1. Initial and recurring attacks, similar but probably more severe than those of type-1, occur in the neighborhood of the genital organs. The initial attack begins with swelling, reddening, and pain in the area surrounding the site of infection with the inflammation developing and extending over the whole groin, thighs and buttocks. This is accompanied by a low-grade fever, mild flu-like symptoms and swelling of the lymph glands in the groin. The development of small, blister like sores soon follows over much of inflamed area rapidly becoming grayish yellow and ulcerous. These blisters typically last for about two weeks. The symptoms in recurrent episodes are generally not so severe but nonetheless unpleasant and uncomfortable. The recurrence may occur as often as several times a month.
Aside of its high infectivity and painful and humiliating conditions, genital herpes pose the serious problems to infants born to infected mothers as such infants may become infected during birth. Another serious problem is the supposition that genital herpes in women may lead to cervical cancer. Moreover, as with the type-1 herpes simplex virus, in case of genital herpes, the virus lies dormant in the sacral region, located outside the spinal canal. The Herpes Book, 1-13 (1980), J. P. Tarcher, L.A.
Treatment of genital herpes is primarily by systemic administration of antiviral drugs as described above, for example by IDU and trifluridine (TFT) with all dangers connected with their high cytotoxicity, with ARA-A, another antiviral with somehow lesser toxicity, and acyclovir or bromovinyldeoxyuridine which are both enzyme inhibitors semi-specific to virus replication. All these agents are given primarily systemically and have high probability to cause severe side effects, as discussed above. Moreover, none of these agents is a selective inhibitor of only the herpes simplex virus replication but effects also a replication of normal cells. Therefore, when used in doses large enough to seek and destroy all the active herpes viruses dormant in the sensory ganglia, these compounds may also be highly disruptive to the normal DNA in the host cells in which the virus multiplies. This is highly undesirable effect since the replication of normal cells is also effected. The topically administered acyclovir ointment seems to be effective in the treatment of primary first occurrence of genital herpes infection but has little if any, effect on recurrent genital herpes disease.
Thus, it would be advantageous to have available treatment of genital herpes which would prevent development of painful sores and inflammation in the genital area, prevent their recurrence and yet be innocuous enough toxicologically so that no systemic administration of cytoxic chemical substances is necessary or needed.
Yet another form of viral herpes disease is so called herpes zoster, commonly known as shingles. Herpes zoster is a disease of middle or old age characterized by extreme pain in a limited area of the upper body or face and an outbreak of small pimply blisters in the same area usually along the nerve branches. The herpes zoster is caused by varicella-zoster virus, the same virus that causes chickenpox. Herpes zoster is an acute central nervous system infection involving primarily the dorsal root ganglia and characterized by vesicular eruption and neuralgic pain in the cutaneous areas supplied by peripheral sensory nerves arising in the affected root ganglia in which the inflammatory changes occur.
There is no specific therapy to this extremely painful viral infection. Corticosteroids, if given early, may relieve pain in severe cases. Aspirin and other anti-inflammatories or antiviral agents systemically may alleviate the pain. However, these agents have the same undesirable side effects as discussed previously.
Thus, it would be extremely important to find an agent which would alleviate the pain connected with the symptomatically occurring blisters during herpes zoster attack.
Another viral infection which may severely effect the patient in that it disfigures patient's face is varicella also know as chickenpox caused by varicella virus. This is a rare form of chickenpox in which the eruption leads to a gangrenous ulceration. There is severe scarring (pock marking) following the healing of the ulceration which never disappears and the person's face is forever disfigured. Moreover, there is no treatment known or prevention for the chickenpox or the subsequent scarring.
Consequently, it would be desirable to have available treatment and/or prevention for the gangrenous ulceration before it results in the scars.
Another highly unpleasant and painful conditions are genital warts caused by human papillomavirus (HPV). Not only this condition is unpleasant and painful but it may also contribute to cervical and genital cancers.
Thus, it would be advantageous and highly desirable to provide an effective treatment against genital warts.
The herbal medicine and use of various extracts or portions of plants as curatives for various diseases has been practiced for thousands of years. For example, quinine, an extract from the bark of a tropical tree, was found to be effective and is still used to mitigate the symptoms associated with malaria.
Long before the introduction of modern scientific methods for development of sophisticated therapeutic agents, remedies and treatments were sought for viral diseases, in particular for painful, distressing and recurring lesions of herpes. The common remedies and treatments had a basis in herbal medicine or folk practices and were usually topical preparations applied directly to the sores to relieve pain, itching, oozing, and discomfort. Such remedies as boiled cloves, tea leaves, peppermint oil, clove oil, eucalyptus oil, paste made from cornstarch, honey, slippery elm, comfrey root, myrrh or volcanic ash, cactus sap and milk compresses were among the many concoctions employed to relieve the symptoms of the disease. For the most part, these agents would afford a certain measure of relief where there was none before. None of these agents however, was successful in decreasing the number of recurrence of sores and in completely suppressing the herpetic symptoms. The Herpes Book, 149 (Supra).
It has now been discovered that the active ingredient present in the liquid obtained as a raw material or as an extract from the green hull of the nut of the kukui tree has a very potent and specific antiviral activity which results in extremely fast suppression of initial symptoms if administered before breakout and has an extremely potent healing activity if administered during the breakout. Following the administration of the active ingredient to the patient suffering from viral sores, the healing period of the sore is shortened from 14 to 21 days to 1-2 days when all painful symptoms disappear, to 3-4 days when all signs of breakout are gone.
Kukui nut tree, Aleurites moluccana, also known as candlenut tree, is a native tree in all countries from western Polynesia to southern Asia and is generally found in woods of lower mountain zone, web gushes and valleys, ravines and hanging valleys of tropics and subtropics. In the United States, the kukui tree is found in all islands of Hawaii.
Certain medicinal and other uses of various portions of the kukui nut tree or its nut have been reported, and in particular in native Hawaiian medicine, the kukui nut had many uses. Uncooked kukui nut kernel was used as a laxative and a diuretic. Baked kukui nut kernel in various preparations was used for the treatment of wounds, ulcers, sore throat and asthma. The smoke of the kukui nut shells was even used to reduce the size of a swollen womb. The recipes of a few of the early herbal remedies using kukui nut tree products have been recorded and preserved.
Specifically, the Hawaii Dental Journal, pages 8 and 13 (1986), discloses several uses of kukui nut tree. Kukui flowers, baked kukui nut and sugarcane mixture was used for stomachache and bowel disorders. Kukui bark was used for herbal tea. Chronic ulcers and scrofula were treated with mixture containing kukui meat and kukui nut cooked in kukui leaves. Sap from the kukui nut tree was used to treat bad breath and coated tongue. The juice of the kukui fruit was used as a mouthwash, for the treatment of a fungal infection thrush or moniliasis--and for other superficial internal oral lesions. To collect the juice (sap), the still green fruit was separated from the stem, and a small amount of clear juice which appeared where the stem had been attached, was collected and combined with the juice from several kukui fruit and then used by dipping a finger into the juice and applying it to the superficial oral lesion. While the juice clearly has the astringent properties, the chemical composition of the juice is as yet unknown and its effects on oral fungal infections is still unknown and has not been studied or quantified.
Additional references of general interest include the following:
June Gutmanis, Kahuna LA'AU LAPA'AU, 24-26, 30 and 36, published by Island Heritage, Honolulu, Hawaii (1976).
Hawaiian Herbs of Medicinal Value. translated by K. Acana in 1972.
All of the publications cited and/or described herein are expressly incorporated by reference and made part of this application.
While the certain therapeutic properties of the juice of the kukui nut hull are known, there has been no reports or suggestions regarding the use of the active ingredient present in the juice from the green hull of kukui nut to treat general viral infections, such as herpes simplex, herpes zoster, genital herpes, genital warts, chickenpox, or the like.
The present invention discloses until now unknown therapeutic and prophylactic effect of the active ingredient present in the kukui nut hull extract and a composition therefor for treatment of viral infections.